Standard and increased canakinumab dosing to quiet macrophage activation syndrome in children with systemic juvenile idiopathic arthritis

ObjectiveMacrophage activation syndrome (MAS) is a life-threatening, potentially fatal condition associated with systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) is a key cytokine in the pathogenesis of sJIA MAS. Many cases of MAS are medically refractory to traditional doses of biologic cytokine inhibitors and may require increased dosing. When MAS occurs in the setting of sJIA treated with the IL-1 receptor antagonist (IL-1Ra), anakinra, increased anakinra dosing may be beneficial. Increased dosing of another IL-1 inhibitor, canakinumab, a monoclonal antibody to IL-1β, has not been reported to treat refractory MAS in the setting of sJIA.MethodsRetrospective data collection extracted from the electronic medical record focused on canakinumab usage and dosing in 8 children with sJIA who developed MAS at a single academic center from 2011 to 2020.ResultsEight sJIA children (five girls) with median age 8.5 years (range, 0.9–14.2 years) were included in the present study. Five children developed MAS at disease onset and three during ongoing canakinumab therapy. MAS resolved in all eight children with canakinumab treatment. When the canakinumab dosing was insufficient or MAS developed during canakinumab therapy, the dosing was temporally up-titrated (four patients, maximum 300 mg per dose) without observed side effects.ConclusionThis report provides evidence for the efficacy and safety of short-term increased doses (2–3-times normal) of canakinumab in treating sJIA associated MAS. Further study of the efficacy and safety of increased doses of canakinumab for treatment of MAS in children with sJIA is warranted

ETANERCEPT TREATMENT RESULTS IN CHILDREN WITH NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS: REMISSION, RECRUDESCENCE, AND ADVERSE EVENTS. RETROSPECTIVE COHORT STUDY

Background. Etanercept is a biological drug most commonly used in patients with juvenile idiopathic arthritis (JIA). The results of its use are showed in local studies.Objective. Our aim was to evaluate the efficacy and safety of the use of etanercept in children with non-systemic JIA, to determine the predictors of remission and the risk factors for the development of exacerbations.Methods. In a retrospective cohort study, the results of etanercept treatment (remission, exacerbations, adverse events) in children with non-systemic JIA were analyzed. The minimum follow-up period was 6 months.Results. The period of remission within 6–36 months occurred in 77/131 (58.8%), exacerbations developed in 18/129 (14.0%) patients. Predictors of achieving remission were the age of JIA onset < 8 years [relative risk (RR) 2.05; 95% confidence interval (CI) 1.27–3.23], the age of prescribing etanercept ≤ 10 years (RR 1.7, 95% CI 1.22–2.38), the time of the disease prior to etanercept prescription < 2.5 years (RR 2.4, 95% CI 1.4–4.4), the presence of HLA-B27 antigen (RR 2.15, 95% CI 0.98–4.75; p = 0.06). The risk of exacerbations was higher in children with polyarticular JIA (RR 2.7, 95% CI 0.9–8.2; p = 0.08), whereas methotrexate therapy reduced the risk of exacerbations (RR 0.32, 95% CI 0.1–1.15; p = 0.05). Etanercept was discontinued due to primary (improvement by the ACRpedi criteria after 3 months of therapy <30%) or secondary (loss of previously achieved ≥ 30% improvement) failure in 14/152 (9.2%) patients; de novo uveitis developed in 8/152 (5.3%) patients; reactions at the injection site — in 6/152 (4.0%) patients.Conclusion. Therapy involving etanercept is more likely to induce remission in younger patients with JIA onset at the age of 8 years and a history of less than 2.5 years. A high risk of exacerbations was noted in patients with polyarticular JIA, and low one — in those receiving methotrexate as a part of combined therapy

The Use of Tocilizumab in 40 Patients With Polyarticular Juvenile Idiopathic Arthritis: the Results of a Retrospective Study

The issue of a therapy of children with juvenile idiopathic arthritis (JIA) with intolerance or insufficient effectiveness of methotrexate remains actual.Objective: Our aim was to study the efficacy and safety of tocilizumab in patients with polyarticular JIA.Methods. In a retrospective study, we studied the results of the use of tocilizumab in patients with active polyarticular JIA ( 5 active joints) resistant to prior therapy with methotrexate or a combination of methotrexate with other nonbiologic disease-modifying antiinflammatory drugs.Results. The data of 40 children (83% girls) with the onset median of polyarticular JIA of 4.8 (2.9, 8.1) years and the interval between the disease onset and the initiation of tocilizumab therapy of 5.7 (1.8, 8.5) years was analyzed. Tocilizumab was used as an intravenous infusion of 8 mg/kg (with a weight 30 kg) or 10 mg/kg (with a weight < 30 kg) every 4 weeks. The duration of tocilizumab monotherapy in 5 (13%) children was 1,109 days (452; 1,542). The stages of inactive disease (according to the criteria of C. Wallace, 2004) in 6 months of tocilizumab therapy reached 6 (15%) patients, in 42 months — 32 (80%) patients. In 3 patients, tocilizumab was canceled due to persistent remission. After 6 months of treatment, there was a marked decrease in erythrocyte sedimentation rate, C-reactive protein concentration, number of leukocytes and platelets (in all cases, p < 0.001) to normal values, which persisted throughout the whole period of drug administration. Predictors for achieving inactive disease were the initial (at the onset of tocilizumab therapy) number of peripheral blood leukocytes < 9.0X109/l [relative risk (RR) 1.92; 95% confidence interval (CI) 0.9–4.6)] and the absence of prior biological therapy (RR 1.92, 95% CI 0.9–4.6). The most frequent side effects of tocilizumab therapy were transient hypercholesterolemia (in 13), hypertriglyceridemia (in 4), transient grade II neutropenia (in 1).Conclusion. The long-term efficacy and relative safety of tocilizumab in children with polyarticular JIA have been showed